Localization of enteroviral RNA within the pancreas in donors with T1D and T1D-associated autoantibodies.
Localization of enteroviral RNA within the pancreas in donors with T1D and T1D-associated autoantibodies.
复制标题
DOI：
10.1016/j.xcrm.2021.100371
复制
发表时间：
2021-08-17
期刊：
影响因子：
--
通讯作者：
Maedler K
中科院分区：
文献类型：
--
作者：
Geravandi S;Richardson S;Pugliese A;Maedler K
肠道病毒感染与自身免疫和1型糖尿病（T1D）有关，但缺乏确定胰腺中单个感染细胞定位的可靠方法。使用基于单分子的荧光原位杂交（smFISH）方法，我们检测到T1D和疾病相关自身抗体（AAb+）的器官供体胰腺中的病毒感染增加。尽管与对照供体相比，在T1D胰腺中以更高的频率发现病毒阳性β细胞，但病毒阳性细胞很少，大多数病毒阳性细胞分散在胰腺外分泌部。在T1D胰腺中增强的CD45+淋巴细胞显示病毒阳性或定位在病毒阳性细胞附近。在T1D供体的脾脏中也发现了更多的感染细胞。AAb+和T1D器官供体胰腺中病毒阳性细胞比例总体增加，表明肠道病毒与临床前和诊断T1D中的免疫细胞浸润、自身免疫和β细胞破坏相关。肠病毒感染的细胞在AAb+和T1D胰腺中显著增加大多数病毒阳性细胞分散在外分泌胰腺内病毒阳性β细胞很少见，但与对照供体相比，T1D供体中的病毒阳性β细胞更多。在患有1型糖尿病（T1D）和疾病相关自身抗体（AAb+）的器官捐赠者的胰腺中发现了显著增加的肠道病毒感染细胞，这些细胞被鉴定为外分泌，内分泌和免疫细胞，并分散在胰腺内。
Enteroviral infections have been associated with autoimmunity and type 1 diabetes (T1D), but reliable methods to ascertain localization of single infected cells in the pancreas were missing. Using a single-molecule-based fluorescent in situ hybridization (smFISH) method, we detected increased virus infection in pancreases from organ donors with T1D and with disease-associated autoantibodies (AAb+). Although virus-positive β cells are found at higher frequency in T1D pancreases, compared to control donors, but are scarce, most virus-positive cells are scattered in the exocrine pancreas. Augmented CD45+ lymphocytes in T1D pancreases show virus positivity or localization in close proximity to virus-positive cells. Many more infected cells were also found in spleens from T1D donors. The overall increased proportion of virus-positive cells in the pancreas of AAb+ and T1D organ donors suggests that enteroviruses are associated with immune cell infiltration, autoimmunity, and β cell destruction in both preclinical and diagnosed T1D. Enterovirus-infected cells are significantly increased in AAb+ and T1D pancreases Most of the virus-positive cells are scattered within the exocrine pancreas Virus-positive β cells are rare but more in T1D compared to control donors Also elevated in T1D donors, there is more infection in spleens than in pancreases By highly sensitive, single-molecule-based fluorescent in situ hybridization for viral RNA, Geravandi et al. found significantly increased enterovirus-infected cells in pancreases from organ donors with type 1 diabetes (T1D) and with disease-associated autoantibodies (AAb+), which were identified as exocrine, endocrine, and immune cells and scattered within the pancreas.
登录
查看更多内容
通过在胰腺淋巴结中发育调节的胰岛细胞抗原的发育表现来启动自身免疫性糖尿病。
DOI：
10.1084/jem.189.2.331
发表时间：
1999-01-18
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Höglund P;Mintern J;Waltzinger C;Heath W;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
30.8
作者：
Barrett, Jeffrey C.;Clayton, David G.;Concannon, Patrick;Akolkar, Beena;Cooper, Jason D.;Erlich, Henry A.;Julier, Cecile;Morahan, Grant;Nerup, Jorn;Nierras, Concepcion;Plagnol, Vincent;Pociot, Flemming;Schuilenburg, Helen;Smyth, Deborah J.;Stevens, Helen;Todd, John A.;Walker, Neil M.;Rich, Stephen S.
通讯作者：
Rich, Stephen S.
影响因子：
48
作者：
Raj, Arjun;van den Bogaard, Patrick;Rifkin, Scott A.;van Oudenaarden, Alexander;Tyagi, Sanjay
通讯作者：
Tyagi, Sanjay
影响因子：
16.2
作者：
Campbell-Thompson, Martha L.;Filipp, Stephanie L.;Haller, Michael J.
通讯作者：
Haller, Michael J.
影响因子：
4.1
作者：
Hodik M;Skog O;Lukinius A;Isaza-Correa JM;Kuipers J;Giepmans BN;Frisk G
通讯作者：
Frisk G